Effect of Low-Dose Rapamycin on Senescence Markers and Physical Functioning in Older Adults with Coronary Artery Disease: Results of a Pilot Study

M. Singh, Michael Dennis Jensen, A. Lerman, S. Kushwaha, C. S. Rihal, B. J. Gersh, A. Behfar, T. Tchkonia, R. J. Thomas, R. J. Lennon, L. R. Keenan, A. G. Moore, James L Kirkland

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

Rapamycin, an mTOR inhibitor affects senescence through suppression of senescence-associated secretory phenotype (SASP). We studied the safety and feasibility of low-dose rapamycin and its effect on SASP and frailty in elderly undergoing cardiac rehabilitation (CR). 13 patients; 6 (0.5mg), 6 (1.0mg), and 1 patient received 2mg oral rapamycin (serum rapamycin <6ng/ml) daily for 12 weeks. Median age was 73.9±7.5 years and 12 were men. Serum interleukin-6 decreased (2.6 vs 4.4 pg/ml) and MMP-3 (26 vs 23.5 ng/ml) increased. Adipose tissue expression of mRNAs (arbitrary units) for MCP-1 (3585 vs 2020, p=0.06), PPAR-γ (1257 vs 1166), PAI-1 (823 vs 338, p=0.08) increased, whereas interleukin-8 (163 vs 312), TNF-α (75 vs 94) and p16 (129 vs 169) decreased. Cellular senescence-associated beta galactosidase activity (2.2% vs 3.6%, p=0.18) tended to decrease. We observed some correlation between some senescence markers and physical performance but no improvement in frailty with rapamycin was noted. (NCT01649960).

Original languageEnglish (US)
Pages (from-to)204-207
Number of pages4
JournalThe Journal of frailty & aging
Volume5
Issue number4
StatePublished - Jan 1 2016

ASJC Scopus subject areas

  • Medicine(all)

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